Trans-1, 2, 3-cyclopropanetricarboxamides and their synthesis



United States Patent Ofiice 3,352,91e Patented Nov. 14, 1 967 ABSTRACTOF THE DISCLOSURE The compounds are of the class oftrans-1,2,3-cyclopropanecarboxamides whose nitrogen atoms aretri-substituted, the synthesis of which being the reacting of potassiumtert. butoxide with an N,N-substituted a-chloroacetamide in the presenceof an inert organic solvent. These compounds are useful as fungicides.

This'invention relates to the synthesis of trans-1,2,3,-cyclopropanetricarboxamides which materials are useful in the control ofpathogenic fungal organisms which attack the foliage of growingvegetation.

In accordance with this invention it has been found thattrans-1,2,3-cyclopropanetricarboxamides of the formula wherein A isalkyl of from 1 to 4 carbon atoms and wherein B is phenyl or alkyl offrom 1 to 4 carbon atoms can be readily prepared by reacting potassiumtext-butoxide with an m-chloroacetamide of the formula CICH:CO.N

wherein A and B have the aforedescribed significance in the presence ofan inert organic solvent.

Among the a-chloroacetamide reactants which provide for thetrans-l,2,3-cyclopropanetricarboxamides of this invention areN,N-dimethyl-a-chloroacetamide N,N-diethyl-:x-chloroacetamideN,N-diisopropyl-a-chloroacetamide N,N,-di-n-butyl-a-chloroacetamideN-methyl-Nethyl-a-chloroacetamide N-methyl-N-n-butyl-a-chloroacetamideN-methyl-N-phenyl-a-chloroacetamide N-ethyl-N-phenyl-a-chloroacetamideN-sec.-butyl-N-phenyl-a-chloroacetamide The reaction temperature canwidely vary as long as it provides for a fluid system, that is atemperature above the freezing point of the system up to and includingthe systems boiling point. In general, however, a reaction temperaturein the range of from about 0 C. to about C. will provide optimumresults. In general atmospheric pressure will be employed, however,pressures above or below atmospheric pressure can be employed.

To illustrate this invention but not lirnitative thereof is thefollowing.

Example I To a suitable reaction vessel equipped with a thermometer andagitator is charged 5.6 parts by weight (substantially 0.05 mol) ofpotassium tert.-butoxide and ap proximately 210 parts by weight oftetrahydrofuran. While agitating this mass 9.2 parts byweight,(substantially 0.05 mol) of N-methyl-N-phenyl-a-chloroacetamideis slowly added. Upon completion of this addition the reaction mass isheated at approximately 50 C. for three hours. Thereafter the reactionmass is subjected to vacuum distillation at 20 C. and 25 mm. Thereafterthe residue is extracted with hot methylene chloride and the extractwashed with water and dried over anhydrous magnesium sulfate. Uponevaporating the methylene chloride there is obtained 3.1 parts by weightof trans-N,N,N"-trimethyl- 1,2,3-cyclopropanetricarboxanilide, M.P.209210 C.

Example II To a suitable reaction vessel equipped with a refluxcondenser, thermometer and agitator is charged 18.4 parts by weight(substantially 0.1 mol) of N-methyl-N-phenylwchloroacetamide,approximately 41 parts by weight of cyclohexene and approximately 144parts by weight of diethyl ether. While agitating 16.8 parts by weight(substantially 0.15 mol) of potassium tert.-butoxide is slowly added.Upon completion of this addition the reaction mass is agitated for abouttwo hours while maintaining the temperature below 40 C. The mass is thenrefluxed for 30 minutes. The reaction mass is then cooled by theaddition of approximately 100 parts by weight of cold water andfiltered. The filter cake is then recrystallized from a mixture ofmethylene chloride and hexane to give 163 parts by weight oftrans-N,'N',N"-trimethyl-1,2,3-cyclopropanetricarboxanilide, M.P.209-210 C.

Example III Employing the procedure of Example I but replacing N-methylN-phenyl-a-chloroacetarnide with an equimolecular amount ofN-ethyl-N-phenyl-a-chl'oroacetamide there is obtainedtrans-N,N',N"-triethyl-l,2,3-cyclopropanetricarboxanilide.

Example IV Employing the procedure of Example II but replacing-methyl-N-phenyl-a-chloroacetamide with an equimolecular amount ofN-isopropyl-N-phenyl-a-chloroacetamide there is obtainedtrans-N,N',N"-triisopropyl-l,2,3-cyclopropanetricarboxanilide.

Example V Employing the procedure of Example I but replacingN-methyl-N-phenyl-a-chloroacetarnide with an equimolecular amount ofN-isobutyl-N-phenyl-a-chloroacetamide there is obtainedtrans-N,N',N"-trilsobutyl-1,2,3-cyclopropanetricarboxanilide.

Example VI To a suitable reaction vessel equipped with a refluxcondenser, thermometer and agitator is charged approximately 70 parts byweight of tetrahydrofuran and 18.6 parts by weight of potassiumtert.-butoxide (substantially 0.1 mol) in the form of a fifty-fiftymixture with tert. butanol. While agitating 12.1 parts by weight(substantially 0.1 mol) of N,N-dirnethyl-a-chloroacetamide is addeddropwise while maintaining the temperature at about C. The mass is thenagitated at about 0 C. for 30 minutes and then refluxed for 30 minutes.The mass is then filtered and the tetrahydrofuran evaporated undervacuum. The residue is then placed on a column of neutral alumina packedwet with pentane. Elution with pentane gives liquid fractions which arecombined and subjected to distillation at 20 C. and 25 mm. The residueis then recrystallized from a mixture of hexane and methylene chlorideto give trans-N,-N,N',N,N",N-hexarnethyl1,2,3-cyclopropanetricarboxamide, M.P. 116-118" C.

Example VII Employing the procedure of Example VI but replacingN,N-dimethyl-a-chloroacetamide with an equimolecular amount ofN,N-diethyl-a-chloroacetamide there is obtained transN,N,N,N',N",N-hexaethyl-1,2,3-cyclopropanetricarboxarnide.

Example VIII Employing the procedure of Example VI but replacingN,N-dimethylaz-chloroacetamide with an equimolecular amount ofN-methyl-N-ethyl-a-chloroacetamide there is obtained trans N,N',N"-triethyl-N,N',N"-trimethyl- 1,2,3-cyclopropanetricarboxamide.

Example 1X Employing the procedure of Example II. but replacingN-methyl-N-phenyl-a-chloroacetarnide with an equimolecular amount ofN,N-di-n-butyl-a-chloroacetarnide there is obtainedtrans-N,N,N',N,N",'N"-hexa-n-b-utyl 1,2,3-cyclopropanetricarboxamide.

Example X Employing the procedure of Example II but replacingN-methyl-N-phenyl-a-chloroacetamide with an equimolecular amount ofN-isobutyl-N-methyl-a-chloroacetamide there is obtainedtrans-N,-N',N"-triisobutyl-N,N',N"-tri-- 4 What is claimed is: 1. Atrans-l,2,3-cyclopropanecarboxamide of the formula wherein A is alkyl offrom 1 to 4 carbon atoms and wherein B is selected from the groupconsisting of phenyl and alkylot from 1 to 4 carbon atoms.

2. Trans-N,N',N"-trirnethyl-1,2,3 cyclopropanetricarboxanilide.

3. Trans-N,N',N"-triethyl 1,2,3 cyclopropanetricarboxanilide.

4. Trans N,N,N,N',N",N" hexamethyl-l,2,3-cyclopropanetricarboxamide.

5. Trans-N,N,N,N',N",N"-hexaethyl-1,2,3 cyclopropanetricarboxamide.

6. A method of making a compound of claim 1 which comprises reactingpotassium tertbutoxide with an achloroacetamide of the formula ClCHzCO.N

wherein A is alkyl of from 1 to 4 carbon atoms and wherein B is selectedfrom the group consisting of phenyl and alkyl of from 1 to 4 carbonatoms in the presence of an inert organic solvent.

7. A method of making trans-N,N',N"-trimethyl-l,2,3-cyclopropanetricarboxanilide which comprises reacting po tassiumtert.-butoxide with N-methyl-N-phenyl-a-chloroacetamide in the presenceof an inert organic solvent.

8. A method of making trans-N,N,N,N',N",N"-hexamethyl 1,2,3cyclopropanetricarboxamide which comprises reacting potassiumtert.-butoxide with N,N-dirnethyl-a-chloroacetamide in the presence ofan inert organic solvent.

References Cited Hoffman et al.: Jour. Amer. Chem. Soc., vol. 74, pp.5485-7 (1952).

WALTER A. MODANC-E, Primary Examiner.

N. TROUSOF, Assistant Examiner.

1. A TRANS-1,2,3-CYCLOPROPANECARBOXAMIDE OF THE FORMULA
 6. A METHOD OFMAKING A COMPOUND OF CLAIM 1 WHICH COMPRISES REACTING POTASSIUMTERT.BUTOXIDE WITH AN ACHLOROACETAMIDE OF THE FORMULA